Chronic toxicity of the adamantane-1-ammonium salt of 2-(5-(adamantane-1-yl)-4-phenyl-1,2,4-triazole-3-thio)acetic acid substance
DOI:
https://doi.org/10.15587/2519-4852.2016.87466Keywords:
chronic toxicity studies, preclinical trials, 1, 2, 4-triazole, adamantine, experiments in animals, remediesAbstract
Nowadays, only seven adamantane derivatives have passed clinical trials as remedies applied for treatment of acne vulgaris, Alzheimer's disease, type 2 diabetes, and as antiviral drugs. The other are on the development stage as potential therapeutic agents for the treatment of diseases caused by iron overload, malaria, tuberculosis, neurological and oncological diseases, and as antioxidant and anti-inflammatory agents.
The aim of our research was to study chronic toxicity of adamantane-1-ammonium salt of 2-(5-(adamantane-1-yl)-4-phenyl-1,2,4-triazole-3-thio)acetic acid to obtain information on the toxicity syndrome and the further research as a promising drug.
Methods. Chronic toxicity study of adamantane-1-ammonium salt of 2-(5-(adamantane-1-yl)-4-phenyl-1,2,4-triazole-3-thio)acetic acid substance was carried out in accordance to requirements concerning preclinical study of new drugs. While selecting the doses of the studied substance, we were guided by the data of preclinical studies of specific activity and results of SD50 and LD50 determination.
The experimental animals were kept in a separate room and were randomly divided into groups of 7 animals. The animals had a standard diet, getting the additive throughout the experiment. The substance was administered in the form of aqueous suspension. The control group got purified water in the same volume. The animals didn’t receive any meal 16 hours before administration of the substance; they got the remedy and the placebo at the same time.
Results. During the chronic experiment, no deaths of the rats and evidence toxicity manifestations were observed. Any deviations of appearance parameters, behavior, eating and drinking, connected with 2-(5-(adamantane-1-yl)-4-phenyl-1,2,4-triazole-3-thio)acetic acid use, were not observed. Also, no significant changes or side effects, connected with the substance administration, were found.
Conclusion. Preclinical trials of adamantane-1-ammonium salt of 2-(5-(adamantane-1-yl)-4-phenyl-1,2,4-triazole-3-thio)acetic acid toxicity has shown, that it is well tolerated by the animals, does not show toxic action signs, and no deaths were observed.
The given substance by the toxic safety nature is promising for the further research as a potential drugReferences
- Blanpied, T. A. (2005). Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block. Journal of Neuroscience, 25 (13), 3312–3322. doi: 10.1523/jneurosci.4262-04.2005
- Maugh, T. (1979). Panel urges wide use of antiviral drug. Science, 206 (4422), 1058–1060. doi: 10.1126/science.386515
- Sonnberg, L. (2003). The Complete Pill Guide: Everything You Need to Know about Generic and Brand-Name Prescription Drugs. Barnes & Noble Publishing, 87.
- Ebtehal Suliman Al Abdullah. (2007). Synthesis and biological testing of new 1-adamantyl derivatives. Riyadh, Saudi Arabia, 147.
- Skolimowski, J. (2003). Synthesis and antioxidant activity evaluation of novel antiparkinsonian agents, aminoadamantane derivatives of nitroxyl free radical. Bioorganic & Medicinal Chemistry, 11 (16), 3529–3539. doi: 10.1016/s0968-0896(03)00299-2
- Zakon Ukrai'ny «Pro likars'ki zasoby» (1996). Verhovna Rada Ukrai'ny, # 123/96-VR. Available at: http://zakon2.rada.gov.ua/laws/show/123/96-vr
- Nakaz Ministerstva ohorony zdorov’ja Ukrai'ny «Pro zatverdzhennja Porjadku provedennja doklinichnogo vyvchennja likars'kyh zasobiv ta ekspertyzy materialiv doklinichnogo vyvchennja likars'kyh zasobiv» (2009). MOZ Ukrai'ny, # 944. Available at: http://zakon3.rada.gov.ua/laws/show/z0053-10
- Pinto, L. H., Holsinger, L. J., Lamb, R. A. (1992). Influenza virus M2 protein has ion channel activity. Cell, 69 (3), 517–528. doi: 10.1016/0092-8674(92)90452-i
- Al-Deeb, O., Al-Omar, M., El-Brollosy, N., Habib, E., Ibrahim, T., El-Emam, A. (2011). Synthesis, Antimicrobial, and Anti-inflammatory Activities of Novel 2-[3-(1-Adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl]acetic Acids, 2-[3-(1-Adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl]propionic Acids and Related Derivatives. Arzneimittelforschung, 56 (01), 40–47. doi: 10.1055/s-0031-1296699
- Kadi, A. A., El-Brollosy, N. R., Al-Deeb, O. A., Habib, E. E., Ibrahim, T. M., El-Emam, A. A. (2007). Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. European Journal of Medicinal Chemistry, 42 (2), 235–242. doi: 10.1016/j.ejmech.2006.10.003
- Giacino, J. T., Whyte, J., Bagiella, E., Kalmar, K., Childs, N., Khademi, A. et. al. (2012). Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury. New England Journal of Medicine, 366 (9), 819–826. doi: 10.1056/nejmoa1102609
- Kumar, C., Kwong, H., Mah, S., Chia, T., Loh, W.-S., Quah, C. et. al. (2015). Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives. Molecules, 20 (10), 18827–18846. doi: 10.3390/molecules201018827
- Lepahin, V. K., Astahova, A. V., Ushkalova, E. A., Illarionova, T. S., Fitilev, S. B., Shkrebneva, I. I. (2008). Razrabotka metodov izuchenija i profilaktiki oslozhnenij farmakoterapii. Moscow: RUDN, 225.
- Stefanov, O. V. (Ed.) (2001). Doklinichni doslidzhennja likars'kyh zasobiv. Kyiv: Vyd. dim "Avicena", 527.
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Copyright (c) 2016 Віра Миколаївна Одинцова, Андрій Володимирович Абрамов, Ігор Федорович Бєленічев
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